Mutants of Streptococcus mutans have been isolated which lack the enzyme activity L (plus)-lactate dehydrogenase. Various studies which have been performed both in the laboratory and using rodent models have shown that these mutants are considerably less cariogenic than naturally occurring strains of Strep. mutans. In addition, it has been shown using rodents that colonization of the oral cavity by a mutant strain provides a significant degree of protection against subsequent infection by naturally occurring strains of this microorganism. These results suggest the potential usefulness of LDH-deficient mutants in serving as effector strains in the replacement therapy of dental caries. The proposed research entails experiments designed to test this hypothesis in a more definitive manner prior to the initiation of human clinical trials. In particular, there will be a year long study using conventional Sprague-Dawley rats in which animals colonized by a mutant strain will be compared to parent infected and control animals with regard to changes in the oral microbial flora, periodontal bone loss, and the incidence and severity of dental caries. In a second study, the pathogenic potential of parent and mutant strains will be compared in a similar fashion using an animal model more closely resembling man, namely the irus monkey. Pending the outcome of these studies, an experiment has been designed to determine an effective means of establishing a mutant strain in the oral cavity of monkeys previously colonized with a naturally occurring strain of Strep. mutans. The proposed approaches involve scaling and pumicing of teeth, and treatment with various disinfecting agents prior to exposure to a concentrated cell suspension of the mutant. Finally, experiments are described which will serve to further characterize the nature of the metabolic and physiologic changes which occur in Strep. mutans as a result of deficiency in LDH catalytic activity, and the mechanism whereby colonization of an oral cavity by the mutant protects against subsequent infection with naturally occurring strains of Strep. mutans.